JP6559245B2 - Method for producing lactide - Google Patents

Description

The present invention relates to a method for producing lactide.

Lactide is conventionally well known as a starting material for polylactide polymers (also denoted as polylactic acid or PLA). PLA is used in pharmaceutical applications such as biodegradable sutures, clamps, osteosynthesis plates, and biologically active controlled release devices. Furthermore, PLA is an attractive polymer for many applications, such as packaging. This is because PLA is biodegradable and can be obtained from renewable sources.

Conventionally, lactide is produced from lactic acid by a method comprising a step of polymerizing lactic acid to form a lactic acid oligomer and a step of depolymerizing the lactic acid oligomer in the presence of a catalyst to form lactide. Lactic acid can be obtained from a number of sources, for example by subjecting a hydrocarbon source to a fermentation medium to produce lactic acid and isolate the lactic acid.

There is a need in the art for a process for producing lactide that results in the efficient production of lactide with high production rates and good product quality to make PLA an attractive alternative to petroleum-derived polymers. Has been. The present invention provides such a method.

The present invention includes the following steps:
Preparing a solution of lactic acid in a volatile organic solvent;
Subjecting the solution to an evaporation step to remove volatile organic solvent and water to form a composition comprising a lactic acid oligomer;
The present invention relates to a process for producing lactide comprising adding a catalyst to a composition containing the lactic acid oligomer and subjecting the mixture to reaction conditions to form lactide.

The method according to the invention has been found to have a number of advantages.

First, starting the lactide production process from a solution of lactic acid in an organic solvent also has process advantages in terms of the overall cost-effective method of producing lactide. This is explained in more detail below. In addition, surprisingly, synthesizing lactide from a solution of lactic acid in a volatile organic solvent gives practically good results and has a higher reaction rate than synthesizing lactide from a solution of lactic acid in water. It turns out that it can even bring.

FIG. 1 shows the percentage of lactide produced from the prepolymer over time for the system of Example 1 (reference aqueous system) and the system of Example 2 (based on MIBK according to the invention). FIG. 2 shows the percentage of lactide produced from the prepolymer over time for the system of Example 1 (reference aqueous system) and the system of Example 4 (system based on MTBE according to the invention).

1 and 2, it can be seen that the system according to the invention exhibits a higher reaction rate than the comparative system. This can be used in overall process configuration and equipment design to reduce costs.

As mentioned above, the method according to the invention is associated with process advantages. To illustrate this, a conventional method for producing lactic acid is first described.

Lactic acid is often produced by fermentation. During fermentation, a base is often added to neutralize lactic acid and keep the pH in a range suitable for microorganisms that produce lactic acid. This results in a fermentation broth containing lactate. Lactate is typically converted to lactic acid by acidification with a strong inorganic acid. This can be done directly on the fermentation broth, but it can also be done after removing the biomass therefrom and optionally after further purification steps. This result is one or more additional results resulting from lactic acid, the salt (dissolved or solid) resulting from the acidification step (anion from lactate cation and acid), and optional additional ingredients such as fermentation broth. An aqueous solution containing components.

There are numerous ways in which lactic acid is isolated and purified starting from this aqueous medium. Examples of these include distillation and extraction. When an extraction step is used, the fermentation medium is often contacted with an organic solvent after various purification steps, such as biomass removal, to form a solution of lactic acid in the organic solvent. This solution is conventionally treated in one of two ways. As a first possibility, a solution of lactic acid in an organic solvent is subjected to a back extraction step by contacting it with water. This is described, for example, in WO 00/17378 pamphlet. The above document describes the use of amines, alcohols and ethers, preferably isoamyl alcohol, diisopropyl ether and Alamine 336 (a high boiling tertiary amine with low water solubility).

WO 95/03268 discloses a feed comprising a carboxylic acid, such as lactic acid, having at least 4-12 carbon atoms and selected from the group consisting of hydroxyl, ester, keto, ether, carbonyl and amide. Extraction with an oxygen-containing solvent having one functional group is described. The solvent extract is then back extracted with an aqueous liquid. Furthermore, WO 2013/093028 uses an organic solvent selected from the group consisting of C5 + ketones, diethyl ether and methyl-t-butyl ether from an aqueous mixture comprising lactic acid and at least 5% by weight of magnesium chloride. To extract lactic acid. The lactic acid solution is subjected to a back extraction step by contacting it with water to form an aqueous lactic acid solution. In the method of this document, the combination of extraction and back-extraction makes it possible to obtain a lactic acid product solution that is more concentrated than the lactic acid starting solution.

In addition to back extraction, it is also described that lactic acid is extracted from an aqueous solution using a volatile solvent and then the solvent is removed. For example, US Pat. No. 2,710,880 describes extracting lactic acid from an aqueous medium containing lactic acid and dissolved salts using an alcohol or ketone having 3 to 4 carbon atoms. Yes. In the examples, the solvent is removed by distillation. GB-A-173479 describes a similar method.

GB-A-2 809 969 describes a process in which sulfuric acid and sodium lactate are added to an 80% lactic acid solution and the solution is extracted with ether. The extract is washed with water to remove contaminants. It has been shown that ethers can be removed and reused in a “well known manner”.

In the method according to the invention, rather than subjecting the extraction solvent containing lactic acid to a back extraction or distillation step to recover lactic acid and convert the lactic acid into a lactic acid oligomer, a solution of lactic acid in a volatile organic solvent. Are used directly as starting materials in the production of lactide, which leads to savings in both equipment investment and processing costs. Furthermore, it has been surprisingly found that the process according to the invention results in lactide formation in good yield, without formation of undesirable by-products and even with a reaction rate that can be increased.

In addition, US Patent Application Publication No. 2009/0093034 describes that lactic acid is a solvent selected from fermentation broth having a pH of 4.8 or less, toluene, xylene, mesitylene, ethylbenzene, methanol, ethanol, propanol, butanol and mineral spirits. The method of extracting using is described. It is described that oligolactic acid can be obtained by heating a lactic acid fermentation medium having a pH of 4.8 or less under reduced pressure and washing with water. Also, the solvent described above is added to the fermentation medium, and the solvent-containing fermentation medium is heated to a temperature between the azeotrope of the solvent and water and the boiling point of the solvent to form a lactic acid oligomer, and A method is also described in which oligolactic acid is extracted from the fermentation medium by heating to a temperature in the range of 60 ° C. to the boiling point of the solvent. This document does not specifically describe the direct conversion of the product to lactide.

US 2012/0116100 describes a process for the preparation of hydroxycarboxylic acid cyclic dimers involving the depolymerization of hydroxycarboxylic acid oligomers. Here, in the depolymerization step, the reaction solution is heated through heat transfer from the heating medium passage under reduced pressure while flowing through the reaction solution passage provided horizontally. The use of volatile organic solvents is not described.

U.S. Patent Application Publication No. 2011/0155557 describes a process for producing lactide from lactic acid oligomers, the process comprising heating the lactic acid oligomers at a temperature of 150-300 ° C. in the presence of a catalyst. Including. The use of volatile organic solvents is not described.

WO 2012/110117 describes a process for producing polyhydroxycarboxylic acids, in particular polylactic acid, via a ring-opening polymerization process using lactide as a starting material. Lactide is removed from the polymer product and recycled to the starting point of the reaction. The production of lactide by a process involving the use of volatile organic solvents is not described.

US Pat. No. 5,420,304 describes an integrated method for preparing cyclic esters via a sequential extraction / reaction process using multiple solvents. The formation of lactic acid oligomers by evaporation of volatile organic solvents and water and subsequent lactide formation by addition of a catalyst is not described.

The invention and its various embodiments are described in more detail below.

The first step in the process according to the invention is to prepare a solution of lactic acid in a volatile organic solvent.

Within the context of the present invention, an organic solvent is volatile when it has a boiling point under atmospheric pressure of less than 200 ° C. Solvents suitable for use in the present invention are required not to react with lactic acid under the conditions that would be encountered in the process according to the present invention. Thus, the solvent should not contain a substantial amount of alcohol. This is because alcohol can react with lactic acid under the formation of lactate esters. Also, the solvent should not contain a substantial amount of amine. This is because amines can react to form lactate amines.

It is preferred that the solvent comprises less than 5%, especially less than 2%, more particularly less than 1% by weight of the combined alcohol and amine.

More preferably, the solvent does not contain a substantial amount of ester. This is because the ester can be hydrolyzed. Accordingly, it is preferred that the solvent comprises less than 5% by weight of ester, especially less than 2% by weight, more particularly less than 1% by weight.

Furthermore, it is preferred that the solvent used in the present invention has a relatively high solubility for lactic acid. This allows the preparation of a relatively high concentration of lactic acid in the solvent, for example at least 5% by weight, in particular at least 10% by weight. Otherwise, the use of very high solvent volumes will be required. For this reason, the use of linear alkanes is not considered well suited. The same applies to aromatic compounds such as toluene, xylene, mesitylene and ethylbenzene. Preferred solvents for use in the present invention are those selected from the group comprising C2-C10 ketones and C2-C10 ethers.

Particularly preferred solvents for use in the present invention are those selected from the group comprising C2-C8 ketones and C2-C6 ethers. The use of methyl isobutyl ketone, methyl ethyl ketone and 2- or 3-pentanone has been found to be particularly attractive.
Mixtures of compounds can also be used.

As mentioned above, the solution of lactic acid in a volatile organic solvent preferably has a lactic acid concentration of at least 5% by weight, in particular at least 10% by weight. Since the solvent evaporates anyway, there is no maximum lactic acid concentration. Higher lactic acid concentrations, and therefore less solvent content, require less solvent evaporation, which would be attractive from a commercial point of view. From a practical point of view, the lactic acid concentration will generally be less than 40% by weight.

A solution of lactic acid in a volatile organic solvent may contain additional components. In particular, it may contain water. This is especially true if the solution is derived from an extraction process. Since water must be removed for lactide production, it is preferred that the amount of water be relatively low. In particular, the water content of the lactic acid solution in the volatile organic solvent is preferably less than 15% by weight.

In one embodiment, a solution of lactic acid in a volatile organic solvent is obtained by extracting lactic acid from an aqueous medium, or contacting the aqueous medium with the organic solvent, and subjecting the resulting reaction medium to a liquid-liquid separation step. It is obtained by attaching. This will be discussed in more detail herein.

A solution of lactic acid in a volatile organic solvent is subjected to an evaporation step to remove the organic solvent and water to form a composition containing lactic acid oligomers.

The evaporation step can be performed using a conventionally known method. For example, it can be performed at elevated temperature, atmospheric pressure, or under reduced pressure. The advantage of doing under reduced pressure is that lower temperatures can be applied. The use of lower temperatures can be attractive to reduce lactic acid racemization.

The evaporation step forms a composition containing lactic acid oligomers. Lactic acid oligomers generally have an average degree of polymerization of 2-30, in particular 4-20, more particularly 5-15. An average degree of polymerization in this range maintains the viscosity at an acceptable level by limiting the amount of volatile low molecular weight oligomers on one side and the amount of very high molecular weight oligomers on the other side. It is thought that a balance is found between them. In the context of this specification, the average degree of polymerization is defined as follows:

DP = 1 + (1000 / (FA * 10/90) -90) / 72

In this formula, DP represents the average degree of polymerization and FA represents the free acid content (wt%) determined by titration.

The composition may further comprise a residual solvent, for example a solvent in the range of 0-5% by weight, in particular 0-2% by weight, in particular 0-0.5% by weight.

The composition may further comprise water, for example in the range of 0-5% by weight, especially 0-2% by weight, more particularly 0-0.5% by weight.

A catalyst is added to the composition containing the amount of lactic acid oligomer. The catalyst catalyzes the depolymerization / cyclization process where the lactic acid oligomer is converted to lactide. Suitable catalysts are known in the art and include organometallic compounds derived from metal oxides, metal halides, metal dusts, carboxylic acids, and the like, and organic compounds such as guanidine. The use of a catalyst containing tin (II) is considered preferred. The catalyst may comprise, for example, tin (II) oxide or tin (II) 2-ethylhexanoate, which are conventionally well known for this purpose. The catalyst can be added in an amount of 0.01 to 5% by weight, in particular 0.01 to 2% by weight, calculated for example based on the amount of lactic acid oligomer.

The reaction mixture is then subjected to reaction conditions to form lactide. Suitable reaction conditions include temperatures in the range of 160-220 ° C, in particular in the range of 180-200 ° C, and pressures in the range of 1-15 mbar. After formation, the lactide evaporates and can be collected, for example, by condensing into a condenser. Higher boiling lactic acid oligomers do not evaporate. Accordingly, lactide can be obtained with high purity.

The lactide obtained by the method according to the present invention can be further processed by conventionally known methods. Depending on the intended future use, purification steps such as crystallization or distillation may be desirable.

Lactide (sometimes referred to as dilactide) is a cyclic dimer of lactic acid. Lactic acid exists in two forms (called D-lactic acid and L-lactic acid) that are optically enantiomers. L-lactic acid is a type that exists mainly in nature, and is generally a type obtained by a fermentation process. The presence of the two types of lactic acid means that the lactide consists of two L-lactic acid molecules, two D-lactic acid molecules, or a combination of L-lactic acid molecules and D-lactic acid molecules forms a dimer. Produces three types of lactide, depending on what you do. These three dimers are called L-lactide, D-lactide and meso-lactide, respectively. Furthermore, a 50/50 mixture of L-lactide and D-lactide having a melting point of about 126 ° C. is often referred to in the literature as D, L-lactide.

The optical activity of lactic acid and lactide is known to change under certain conditions, and when equal amounts of D-enantiomer and L-enantiomer are present, there is a tendency towards optically inactive equilibrium. It is known to affect the rate of such racemization when changing the relative concentrations of D- and L-enantiomers in the starting material, the presence of impurities or catalysts, and the temperature and pressure. The optical purity of lactic acid or lactide is critical for the stereochemistry of polylactic acid obtained after ring-opening polymerization of lactide and is a polymerization parameter for polymer properties.

In the method of the present invention, the optical purity of the starting material can be maintained to a relatively high degree. In other words, if the process according to the invention starts with lactic acid having an optical purity of at least 90%, in particular at least 95%, more particularly at least 98.5%, more in particular at least 99.5%, lactide vapors From the reaction mixture with an optical purity of at least 85%, in particular at least 92%, more particularly at least 97.5%, and more particularly at least 99%. The loss of optical purity is preferably less than 5%, in particular less than 3%, more particularly less than 1% and even more particularly less than 0.5%. Here, the loss of optical purity is defined as the difference between the optical purity of the starting lactic acid and the optical purity of the lactic acid present in the lactide when present in the lactide vapor obtained from the reaction mixture.

In the present specification, the displayed optical purity means the proportion of either D-lactic acid or L-lactic acid calculated based on the total amount of lactic acid present in the system. Depending on the process steps, lactic acid will be present in the form of lactic acid, lactic acid oligomers and / or lactide. That is, an optical purity of 90% is calculated based on the total amount of lactic acid molecules present in the system in any form, 90% is L-lactic acid and 10% is D-lactic acid, or 90% It means D-lactic acid and 10% is L-lactic acid.

It is preferred that the lactic acid present in the starting material is L-lactic acid having an optical purity of at least 90%, in particular at least 95%, more particularly at least 98.5%, more particularly at least 99.5%.

In one embodiment, a solution of lactic acid in a volatile organic solvent used as starting material in the process according to the invention is obtained by extracting lactic acid from an aqueous medium. This extraction step can include contacting an aqueous medium containing lactic acid with a volatile organic solvent that is at least partially immiscible with the aqueous medium containing lactic acid. With regard to suitable organic solvents, reference is made to what has been mentioned above.

The lactic acid content of the aqueous medium is preferably as high as possible. For example, the aqueous mixture may comprise at least 5%, preferably at least 10%, more preferably at least 15% by weight lactic acid, based on the total weight of the aqueous mixture. A value of at least 20% by weight, more particularly at least 25% by weight may be particularly preferred. As a maximum, a value of 40% by weight may be mentioned.

In one embodiment, the aqueous mixture has a pH of 2 or less, typically 1 or less, for example 0-1. Preferably, the pH is relatively low and lactic acid is present in acid form in the mixture to allow extraction. The pH can be adapted by the addition of inorganic acids.

In one embodiment, the aqueous medium comprising lactic acid comprises at least 5% by weight dissolved inorganic salt. It has been found that the presence of dissolved inorganic salt results in an improved extraction process in that a greater amount of lactic acid is incorporated into the volatile organic solvent. Furthermore, the presence of dissolved inorganic salt means that the solubility of the organic solvent in an aqueous medium is reduced. This results in less solvent loss during the extraction process, which is attractive from an economic and environmental point of view. Furthermore, the solubility of water in the organic solvent also decreases as the salt concentration increases.

These combined effects result in the potential application of a solvent that is miscible with pure water, but only partially miscible with water containing a substantial amount of salt. This results in a wider range of possible suitable solvents. In order to enhance the effect of the present invention, the salt concentration is preferably relatively high. It may be preferred that the salt concentration is at least 10% by weight, more preferably at least 15% by weight, even more preferably at least 20% by weight. Depending on the lactic acid content of the solution, the salt content may be higher, for example at least 25% by weight, or at least 30% by weight, or in some cases at least 35% by weight. The maximum value is generally determined by the solubility of such salts in such lactic acid solutions and can be readily determined by one skilled in the art.

Inorganic salts suitable for use in the present invention are inorganic salts having a high solubility in water, in particular allowing the salt concentration specified above to be obtained. The cations present in the inorganic salt are preferably selected from magnesium, calcium, potassium, sodium, nickel, cobalt, iron and aluminum and combinations thereof. The use of one or more cations selected from the group of magnesium, calcium, sodium and potassium is preferred. The use of calcium and magnesium is particularly preferred. This is because these cations were found to promote the presence of lactic acid in the organic phase. The use of magnesium may be particularly preferred for this reason.

The anion of the inorganic salt can be selected from, for example, nitrates, sulfates and halides. It will be apparent to those skilled in the art that the anion and cation should be combined in such a way as to obtain a soluble salt. The use of halide salts may be preferred from a practical point of view. The halide salt can be fluoride, chloride, bromide or iodide. The use of chloride is preferred. This selection is true in combination with the preferences for the cations identified above. Specific examples of preferred salts _are MgCl _2, CaCl 2, NaCl and KCl. These salts were found to contribute to the enhanced distribution of lactic acid into the organic phase. The use of calcium chloride and magnesium is considered preferred. The use of magnesium chloride can be particularly preferred.

In the extraction step, the aqueous medium containing lactic acid and preferably the dissolved inorganic salt described above is a condition that ensures intense contact between the organic solvent and generally the solvent and the medium. Together. If present, a system is formed comprising an aqueous layer containing the soluble salt and possibly some residual lactic acid, and an organic solvent phase containing lactic acid.

In the separation step, the aqueous phase and the organic solvent phase are separated from each other by liquid-liquid separation, which can be performed using conventionally known methods for separating liquid-liquid two-phase systems. Examples of devices and methods suitable for liquid-liquid separation include decantation, sedimentation, centrifugation, use of plate separators, use of coalescers, and use of hydrocyclones. Combinations of various methods and devices can also be used.

The separation step can be performed at any suitable temperature, generally in the range of 5 to 95 ° C. Regarding the composition of the solvent phase, reference is made to what has been described above.

In one embodiment, an acidification step wherein an aqueous medium comprising lactic acid and preferably dissolved inorganic salt comprises adding an inorganic acid to lactate to provide an aqueous medium liquid comprising lactic acid and dissolved inorganic salt. Is obtained by a method comprising

The lactate salt can be in solid form, for example in the form of a filter cake or suspension. This may be the case when the lactate salt has a relatively limited water solubility, for example magnesium lactate. On the other hand, the lactate salt can be provided in dissolved form, for example in the case of sodium lactate, potassium lactate and calcium lactate.

The acid used in the acidification step is typically a strong acid such as hydrochloric acid, sulfuric acid or nitric acid. The acid should be selected in such a way that the anion of the acid and the cation of the lactate together form a soluble salt. The use of hydrochloric acid or nitric acid is preferred, and the use of hydrochloric acid is particularly preferred. In this case, an aqueous mixture containing lactic acid and chloride salt is obtained. In a preferred embodiment, the solid form of magnesium lactate is contacted with a hydrochloric acid solution to form an aqueous medium comprising lactic acid and dissolved magnesium lactate.

Acidification can be performed, for example, by contacting lactate (solid or dissolved form) with an aqueous acid solution. In the case of HCl (which can also be gaseous), the lactate solution or suspension can be contacted with a gaseous stream containing HCl.

If the acidification of the lactate is carried out by contacting it with an acidic solution, preferably the acidic solution has as high an acid concentration as possible. Such a high acid concentration results in an aqueous mixture having a high lactic acid concentration, which is desirable. Thus, the acidic solution comprises at least 5 wt%, more preferably at least 10 wt%, and even more preferably at least 20 wt% acid, based on the total weight of the acidic solution.

Acidification is typically performed using an excess of acid. The excess is preferably small so that the aqueous mixture obtained does not have a high acidity. High acidity may be undesirable from the standpoint of further processing such a mixture. For example, the excess of acid used can be such that the resulting aqueous mixture has a pH of 2 or less, preferably a pH of 0-1.

If a gaseous stream comprising HCl is used, the lactate solution or suspension can be contacted with the gaseous stream comprising HCl, for example by blowing it into the lactate solution or suspension. If HCl gas is used, HCl can come from the pyrolysis step as described above.

Preferably, the acidification is performed at a temperature of 75 ° C. or lower. At higher temperatures, it becomes uneconomical to adapt the equipment to the harsh conditions of the acidic environment at high temperatures.

After acidification, the solid material, if present, can be removed from the aqueous mixture, for example, by filtration. The presence of solid material in the aqueous mixture is undesirable during extraction.

The aqueous mixture can be concentrated to a concentration up to the solubility of the inorganic soluble salt after acidification and before extraction.

In one embodiment, lactates derived from the fermentation process are used, in particular calcium lactate, sodium lactate, potassium lactate or magnesium lactate, in particular magnesium lactate. Accordingly, the method of the present invention may further comprise a fermentation process for forming lactic acid, the fermentation process comprising fermenting a carbon source, such as a carbohydrate, by a microorganism in a fermentation broth to form lactic acid, and Neutralizing at least a part of the lactic acid by the addition of a base, in particular a sodium base, a potassium base, a calcium base or a magnesium base, more particularly a magnesium base, thereby obtaining a lactate as defined above, in particular magnesium lactate. Including.

Fermentation processes for producing lactic acid are known in the art and do not require further explanation here. Depending on the desired acid to be produced, the carbon source and the available microorganisms, it is within the skill of the art to select a suitable fermentation process using the common general knowledge of the skilled person.

The product of the fermentation process is a fermentation broth, which is an aqueous liquid containing lactate, biomass and optionally further components such as impurities such as sugars, proteins and salts. The lactate salt can exist in solid form, dissolved form, or both solid and dissolved form. For example, sodium lactate, potassium lactate and calcium lactate are generally present in dissolved form. Magnesium lactate is often present in both solid and dissolved forms, depending on the concentration.

If desired, the fermentation broth can be subjected to a biomass removal step, such as a filtration step, before further processing. This is generally preferred to improve product quality, particularly product color.

Another intermediate step may be to separate the solid reaction product, such as magnesium lactate, from the fermentation broth before, after or simultaneously with biomass removal, and optionally subject the solid product, such as magnesium lactate, to a washing step. . Depending on the concentration, magnesium lactate can precipitate in the fermentation medium. In one embodiment, solid magnesium lactate is separated from the fermentation medium, for example by filtration, and subjected to the acidification step described above.

Another intermediate step may be to subject the fermentation broth to a concentration step to increase the concentration of lactate in the composition prior to acidification. This step can take place before, after or simultaneously with biomass removal. Such a process can be attractive for increasing the content of solid lactate. The solid lactate can then be separated from the fermentation broth as described above and processed in the process according to the invention as a solid lactate, in particular magnesium lactate.

Other intermediate steps, such as purification steps, can be performed as desired, as will be apparent to those skilled in the art.

It will be apparent to those skilled in the art that preferred aspects of the various steps in the method according to the invention can be combined as desired.

The present invention is illustrated by the following examples, but the present invention is not limited to or by the following examples.

Example 1 (comparison)
4520 g of a 9 wt% lactic acid solution in water was prepared. This solution was concentrated to about 90% by weight at a pressure of 100 mbar (a). After concentration, 480 g of concentrated lactic acid solution was obtained. 400 g of concentrated lactic acid solution was heated in a round bottom flask using a mechanical stirrer to a set temperature of 180 ° C. in 90 minutes and slowly depressurized. In 90 minutes the pressure was reduced to 100 mbar (a) while the water had evaporated. The pressure was then further reduced to 50 mbar (a) in the next 60 minutes and finally to 40 mbar (a). A total of 94 g of water was condensed.

The prepolymer in the flask thus produced had a free acid content of 17% by weight as measured by titration. From this number it can be calculated that the average degree of polymerization of the prepolymer is 7.1. HPLC measurements showed that the prepolymer contained 4.1 wt% D-lactide and L-lactide and less than 0.1 wt% mesolactide. The water content of the prepolymer was 0.24% by weight as measured by Karl Fischer titration.

Lactide synthesis was performed directly after the prepolymerization step in the same reactor. First, 0.05 wt% tin 2-ethylhexanoate (catalyst) was added. After the flask contents were heated to 120 ° C. with the prepolymer (263 g), the stirrer was started due to the very high viscosity. The set temperature was then increased to 200 ° C. The vacuum was then reduced to 10 mbar (a). 192 g of lactide was evaporated and condensed in 3.25 hours.

The resulting lactide contained 87.8% by weight D-lactide plus L-lactide and 3.3% by weight meso lactide as determined by HPLC method. HPLC further showed that the remainder of the components were mainly lactic acid, lactoyl lactic acid and lactoyl lactoyl lactic acid. These components are liberated by the catalyst cleaving off the lactide from the regular and irregular oligomers, while having the same boiling point as the lactide and evaporated together with the lactide.

Example 2 (according to the invention)-MIBK as solvent
3977 g of a 10 wt% lactic acid solution in methyl isobutyl ketone (MIBK) containing 2% water was prepared. The solution was concentrated to about 90% by weight at 90 ° C. and 120 mbar (a) pressure. After concentration, 439 g of concentrated lactic acid solution was obtained. 420 g of concentrated lactic acid solution was heated in a round bottom flask using a mechanical stirrer to a set temperature of 180 ° C. in 50 minutes and slowly depressurized. In 60 minutes the pressure was reduced to 100 mbar (a) while water and MIBK were still evaporating. When 100 mbar (a) was reached, little MIBK came to the condensate. This indicates that (almost) all MIBK has evaporated. The pressure was then further reduced to 50 mbar (a) in the next 30 minutes and only 2 ml of condensate was collected.

A total of 117 g water / MIBK was condensed. The free acid content is measured by titration to 12.2% by weight, which gives an average degree of polymerization of 10.

The prepolymer contained 5.2% by weight of D-lactide and L-lactide and less than 0.5% by weight of meso lactide as measured by HPLC. The water content of the prepolymer was determined to be 0.43% by weight by Karl Fischer titration.

The lactide synthesis was performed directly after the prepolymerization step in the same reactor using 296 g of prepolymer. First, 0.05 wt% tin 2-ethylhexanoate (catalyst) was added. The contents of the flask were heated to 200 ° C. with the prepolymer. The vacuum was then reduced to 10 mbar (a). 197 g of lactide was evaporated and condensed in 2.25 hours. The resulting lactide contained 87.3% by weight of D-lactide and L-lactide and 1.5% by weight of meso lactide, with the remainder being lactic acid and higher order oligomers.

FIG. 1 shows the weight of lactide produced from a prepolymer over time for the system of Example 1 (reference aqueous system) and the system of Example 2 (system based on MIBK according to the invention). From FIG. 1 it can be seen that the system according to the invention exhibits a higher reaction rate than the comparative system. This can be used in overall process configuration and equipment design to reduce costs.

Example 3 (According to the Invention) -2096.6 g of a solution of 20% by weight lactic acid (lactic acid crystals, Purac Corbion) in 2-pentanone (Acros) with 2% by weight water as 2-pentanone as solvent is prepared It was done. This solution was concentrated to about 90 wt% in a rotary evaporator under reduced pressure at 80-90 ° C. (1589.3 g of water and 2-pentanone was condensed). After concentration, 449 g of concentrated lactic acid solution was obtained. The solution was transferred to a round bottom flask with a mechanical stirrer and heated to 180 ° C. in 55 minutes. The pressure was reduced slowly to 180 mbar at 180 ° C. In 60 minutes, water and 2-pentanone were further evaporated, and a two-phase system was formed in the condenser cooled at room temperature. After 100 mbar was reached, the pressure was further reduced to 50 mbar and some lactide present in equilibrium in the prepolymer began to evaporate and crystallize in the condenser.

A total of 116 g of water / 2-pentanone was condensed. Of that, 56 g was as an aqueous phase. Based on the total weight, it was estimated that a prepolymer having an average degree of polymerization of 7-8 was obtained. The prepolymer contained 4.7% by weight of D-lactide and L-lactide and 0.4% by weight of meso lactide.

Next, 0.05 wt% tin 2-ethylhexanoate (catalyst) was added. The prepolymer (315 g) was heated to 200 ° C. and the vacuum was slowly reduced to 10 mbar. In 160 minutes, 157.3 g of lactide was distilled off. This is faster than reference. The lactide had a content of D + L lactide of 68.3% by weight. This purity, lower than the reference and MIBK cases, indicates a relatively low DP of the prepolymer and a co-distillation of lactate and lactoyl lactic acid liberated by catalytic depolymerization of the prepolymer. By optimizing the temperature-pressure relationship during prepolymerization, the DP of the prepolymer and consequently the purity of the lactide can be increased. The meso lactide content of lactide was 0.9% by weight.

Example 4 (According to the Invention)-MTBE as Solvent
3505.9 g of a solution of 12 wt% lactic acid (lactic acid crystals, Purac Corbion) in MTBE (methyl t-butyl ether, Acros) containing 4 wt% water was prepared. This solution was concentrated to about 90 wt% in a rotary evaporator under reduced pressure at 80-90 ° C. (3040.3 water and MTBE were condensed). After concentration, 434.9 g of concentrated lactic acid solution was obtained. The solution was transferred to a round bottom flask with a mechanical stirrer and heated to a set temperature of 180 ° C. in 101 minutes. Slow depressurization at 180 ° C. and reduced to 80 mbar in 23 minutes, while water and MTBE were further evaporated. At 80 mbar, some lactide present in equilibrium in the prepolymer began to evaporate and crystallize in the condenser and the prepolymerization was stopped. A total of 110 g water and MTBE were evaporated. It was estimated that a prepolymer having an average degree of polymerization of 7-8 was obtained. The prepolymer contained 4.7% by weight of D-lactide and L-lactide and 0.4% by weight of meso lactide.

Next, 0.05 wt% tin 2-ethylhexanoate (catalyst) was added. The prepolymer (316 g) was heated to 200 ° C. and the vacuum was slowly reduced to 5 mbar. In 153 minutes, 180 g of lactide was distilled off. This is faster than reference. The lactide had a content of 77% by weight D + L lactide. The meso lactide content of lactide was 1.1% by weight.

FIG. 2 shows the weight of lactide produced from the prepolymer over time for the system of Example 1 (reference aqueous system) and the system of Example 4 (MTBE based system according to the present invention). From FIG. 2 it can be seen that the system according to the invention exhibits a higher reaction rate than the comparative system. This can be used in overall process configuration and equipment design to reduce costs.

Example 5 (according to the invention)-MEK as solvent
1680 g of a solution of 25 wt% lactic acid (lactic acid crystals, Purac Corbion) in MEK (methyl ethyl ketone, Acros) containing 10 wt% water was prepared. This solution was concentrated to about 90% by weight in a rotary evaporator at 80 ° C. and 150 mbar pressure (1217 g of water and MEK were condensed). After concentration, 445.5 g of concentrated lactic acid solution was obtained. The solution was transferred to a round bottom flask with a mechanical stirrer and heated to a set temperature of 180 ° C. in 81 minutes. Slow depressurization at 180 ° C. and reduced to 100 mbar in 60 minutes, while water and MEK were further evaporated. Already at 100 mbar some lactide began to evaporate and crystallize in the condenser and the prepolymerization was stopped. A total of 94 g of water and MEK were evaporated. It was estimated that a prepolymer having an average degree of polymerization of 7-8 was obtained. The prepolymer contained 3.5% by weight of D-lactide and L-lactide and less than 0.1% by weight of meso lactide.

Next, 0.05 wt% tin 2-ethylhexanoate (catalyst) was added. The prepolymer was heated to 200 ° C. and the vacuum was slowly reduced to 10 mbar. In 185 minutes, 155 g of lactide was distilled off. This is faster than reference. The lactide had a content of 70% by weight D + L lactide. The meso lactide content of lactide was 1% by weight.

Claims (14)

The following process:
Preparing a solution of lactic acid in a volatile organic solvent;
The solution is subjected to an evaporation step to remove a volatile organic solvent and water to form a composition containing a lactic acid oligomer, wherein the volatile organic solvent is a total of 5% by weight or more of alcohol and amine Free of and the solvent is selected from the group comprising C2-C10 ketones and C2-C10 ethers ,
Adding a catalyst to the composition comprising the lactic acid oligomer and subjecting the mixture to reaction conditions to form lactide;
A process for producing lactide, comprising: The process according to claim 1, wherein the concentration of lactic acid in the solution of lactic acid in the volatile organic solvent is at least 5% by weight. The process according to claim 1 or 2 , wherein the water content of the solution of lactic acid in the volatile organic solvent is less than 15% by weight. The method according to any one of claims 1 to 3 , wherein in the composition containing the lactic acid oligomer, the lactic acid oligomer has an average degree of polymerization of 2 to 30. The composition comprising the evaporation step after forming lactic acid oligomers, containing 0-5 wt% range residual solvent and / or 0 to 5 wt% of the water of any one of claims 1-4 The method described in 1. The process according to any one of claims 1 to 5 , wherein the reaction conditions during the lactide formation step comprise a temperature in the range of 160-220 ° C and a pressure in the range of 1-15 mbar. Lactate of the starting solution is at least 90% optical purity, and lactide vapor is obtained with at least 85% optical purity, the method according to any one of claims 1-6. Loss of the optical purity of lactic acid in the lactide formation reaction is less than 5%, the method according to any one of claims 1-7. In the method according to any one of claims 1-8 is used as a starting material, the solution of lactic acid of a volatile organic solvent is obtained by extraction from the aqueous medium of lactic acid, one of the claims 1-8 The method according to claim 1. The method of claim 9 , wherein the aqueous medium comprising lactic acid comprises at least 5% by weight dissolved inorganic salt. 11. The method of claim 10 , wherein the aqueous medium comprising lactic acid and dissolved inorganic salt is obtained by a method comprising an acidification step comprising adding an inorganic acid to lactate. The method according to claim 11 , wherein the lactate salt is selected from magnesium lactate, calcium lactate, sodium lactate and potassium lactate. The inorganic acid is selected hydrochloric, nitric and sulfuric, the acid, cations of the anion and the acid salt of the acid is chosen so as to form soluble salts together claim 11 or 12 The method described in 1. The method according to any one of claims 11 to 13 , wherein the solution of lactate is derived from a fermentation process.

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